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B H Ginsberg

Publications and source records attributed to B H Ginsberg.

10 recordsLinked to original sources
PubMed1992

An overview of minimally invasive technologies.

Self-measurement of blood glucose is an integral part of diabetes mellitus therapy. As many as 65% of diabetic people (4-5 million people) perform some degree of self-monitoring and approximately 20-30% do so frequently. Most patients consider this the most onerous part of their diabetes therapy. It requires obtaining blood, frequently in public, and is usually the most painful part of therapy, being significantly more painful than insulin self-administration. Patients therefore are anxious for a less-invasive method for glucose measurement. Methods exist or are being developed for minimally invasive glucose monitoring, which use body fluids other than blood (e.g., sweat and saliva), subcutaneous tissue, or blood measured less invasively. Sweat and saliva are relatively easily obtained but their glucose concentration lags significantly behind blood glucose. Methods to increase sweating have been developed and seem to increase the timeliness of the sweat glucose measurement. Subcutaneous glucose measurement seems to lag only a few minutes behind blood glucose and may actually be a better measurement of the critical values of glucose concentrations in brain, muscle, and other tissue. Glucose can be measured by noninvasive or minimally invasive methods, such as those making skin or mucous membranes permeable to glucose or those placing a reporter molecule in the subcutaneous tissue. Needle-type sensors have been improved in accuracy, size, and stability and can be placed into the subcutaneous tissue or peripheral veins to monitor blood glucose with miniature instruments.

Blood Glucose Self-Monitoring↗
PubMed1991

Insulin sensitivity is increased in Friend erythroleukemia cells enriched in polyunsaturated fatty acid.

Increases in membrane lipid unsaturation and drug-induced increases in membrane fluidity have been shown to be associated with increases in insulin receptor concentration in animals, cultured cells, and liposomes. In the current study, we have examined the effect of increased membrane fatty acid unsaturation on insulin action. Friend Erythroleukemia cells were grown with exogenous polyunsaturated fatty acids for three days. After growth in medium supplemented with fatty acids, the unsaturation index of the phospholipids increased from 1.08 to 1.92, and this was associated with a significant decrease in anisotropy, as measured by fluorescence polarization. When measured at 15 degrees C, insulin receptor number rose from 9000 to 22,000 per cell with increased fatty acid unsaturation. The affinity for insulin in the polyunsaturated fatty acid treated cells decreased, however, resulting in similar amounts of insulin binding at low insulin concentrations but more binding at high insulin concentrations when compared to control cells. In contrast, binding of IGF-I was not influenced by increased membrane fatty acid unsaturation. When measured at 37 degrees C there were no changes in binding of insulin or IGF-I. Internalization of insulin was identical in control cells and in cells with increased membrane fatty acid unsaturation. Thymidine incorporation, an insulin-dependent function in these cell, was measured in control and fatty acid treated cells. In control cells, insulin increased thymidine incorporation by 80%, with an ED50 of about 5 nM. In cells treated with polyunsaturated fatty acids, the insulin stimulated thymidine incorporation was slightly higher and the ED50 was about 0.2 nM. In contrast, there was no increase in the sensitivity or responsiveness of fatty acid treated cells to IGF-I. We conclude that increased membrane fatty acid unsaturation greatly influences insulin binding and biological sensitivity, but not that of IGF-I. At low insulin levels, there was a greater insulin bioeffectiveness, despite the same or lower insulin binding, suggesting more efficient coupling of the insulin-effector complex.

Animals↗
PubMed1979

Reconstitution of the solubilized insulin receptor in phospholipid vesicles.

The insulin receptor was solubilized from turkey erythrocyte membranes by extraction with 1% beta-octylglucopyranoside. Insulin binding was enhanced when the solubilized material was reconstituted in phospholipid vesicles. The affinity of the reconstituted vesicles for various insulins was similar to that of the intact membranes: porcine insulin greater than proinsulin greater than desoctapeptide insulin. A curvilinear Scatchard plot was obtained for insulin binding to the reconstituted system at 15 degrees C. A high affinity association constant of 1.4 x 10(9) M-1 was obtained from the Scatchard plot. This is a four-fold increase over the value for the turkey erythrocyte membrane, which contains more highly saturated phospholipids. This suggests that the insulin receptor may be sensitive to the lipid composition of the membranes in which it is embedded.

Animals↗
PubMed1979

Decrease in insulin receptors during Friend erythroleukemia cell differentiation.

The Friend erythroleukemia cell has an insulin receptor with all the properties of mammalian insulin receptors: rapid, reversible, and saturable binding of insulin; specific for insulin and insulin analogs; inversely proportional to temperatures; sharply pH dependent (optimum = 8.0); and demonstrated ligand-induced accelerated dissociation consistent with negative cooperativity. There were 17,200 sites per cell. After induction by dimethylsulfoxide, 80% of the cells became benzidine positive (i.e., contained hemoglobin). The receptor concentration dropped to 4300 sites per cell, while the remaining receptors retained all the initial binding characteristics. This loss of receptors could not be attributed directly to either dimethylsulfoxide or changes in cell size. Thus, during the process of differentiation, the concentration of insulin receptors in the Friend erythroleukemia cell decreases.

Animals↗
PubMed1978

Properties and partial purification of the detergent-solubilized insulin receptor: a demonstration of negative cooperativity in micellar solution.

Turkey erythrocytes possess insulin receptors with binding properties very similar to those of mammalian insulin receptors. In the present study, the insulin receptor of the avian erythrocyte has been solubilized in Triton X-100, extensively characterized and partially purified, and its properties compared to those of the membrane-bound receptor. The solubilized insulin receptor has a Stokes radius of 70 A and an apparent molecular weight of 300 000 in 0.05% Triton. The binding of insulin to the soluble receptor was very similar to the binding observed with the membrane-bound receptor. Thus, binding was markedly temperature dependent for both the soluble and membrane-bound forms, although the kinetics of binding were slower with the soluble receptor. Both forms of the receptor also showed a sharp pH optimum; however, solubilization produced a shift from maximal binding at pH 7.8 to pH 7.3. The soluble receptor also retained insulin analog specificity, ion sensitivity and negative cooperativity. The soluble receptor did not appear to degrade either bound or free insulin. On DEAE-cellulose chromatography the receptor eluted as a single peak. The specific activity of this partially purified preparation was 25--30 pmol/mg protein (about 500-fold enrichment over crude extract and 5-fold over highly purified membranes). Extensive attempts to purify further the receptor by gel filtration, carboxymethyl-cellulose chromatography and affinity chromatography resulted in either a very low yield or only modest enrichment. Purification was also complicated because the receptor was easily denatured; about 40% of the activity was lost after a 90-min exposure to 3 M urea or pH 4.5. These data suggest that the insulin receptor retains its properties in the absence of the lipid bilayer of the membrane. Complete purification will be difficult due to a lack of stability under a number of conditions.

Animals↗
PubMed1977

The insulin receptor of the turkey erythrocyte: similarity to mammalian insulin receptors.

Avian erythrocytes possess insulin receptors which have binding properties that are virtually identical to those of the well studied mammalian insulin receptors. The affinity for porcine insulin was identical for the turkey and mammalian receptors over the entire range of insulin concentrations, as was the affinity of each of four insulin analogues which differed 300-fold in biological potency. Insulin induced acceleration of dissociation (i.e., the negatively cooperativite site-site interaction) was indistinguishable over a 10(6) range of insulin concentrations. Sharp pH dependence of binding was identical for turkey and mammalian receptors. The effects of temperature on association, dissociation and steady state binding were also identical. Thus, although birds and mammals have evolved separately for 300 million years there has been little change in the properties of the insulin receptor over this time period.

Allosteric Regulation↗
PubMed1976

The insulin receptor of the turkey erythrocyte. Characterization of the membrane-bound receptor.

The insulin receptor of the turkey erythrocyte has previously been shown to be very similar to that of the mammalian insulin receptors. As a first step in the isolation of this receptor a highly purified plasma membrane fraction has been prepared. The binding characteristics of the purified membrane-bound receptor were identical to those found with intact erythrocytes, but the membrane preparation had very little insulin-degrading activity. Isolation of the membrane by the methods described gave a 100-fold purification of the insulin receptor with 67% yield.

Animals↗